tbuckley/cabot-search huggingface dataset:
Association between changes in carbohydrate intake and long term weight changes: prospective cohort study
Authors: Yi Wan, Deirdre K Tobias, Kristine K Dennis, Marta Guasch-Ferré, Qi Sun, Eric B Rimm, Frank B Hu, David S Ludwig, Orrin Devinsky, Walter C Willett
Journal: BMJ (2023)

To comprehensively examine the associations between changes in carbohydrate intake and weight change at four year intervals.Prospective cohort study.Nurses' Health Study (1986-2010), Nurses' Health Study II (1991-2015), and Health Professionals Follow-Up Study (1986-2014).136 432 men and women aged 65 years or younger and free of diabetes, cancer, cardiovascular disease, respiratory disease, neurodegenerative disorders, gastric conditions, chronic kidney disease, and systemic lupus erythematosus before baseline.Weight change within a four year period.The final analyses included 46 722 women in the Nurses' Health Study, 67 186 women in the Nurses' Health Study II, and 22 524 men in the Health Professionals Follow-up Study. On average, participants gained 1.5 kg (5th to 95th centile -6.8 to 10.0) every four years, amounting to 8.8 kg on average over 24 years. Among men and women, increases in glycemic index and glycemic load were positively associated with weight gain. For example, a 100 g/day increase in starch or added sugar was associated with 1.5 kg and 0.9 kg greater weight gain over four years, respectively, whereas a 10 g/day increase in fiber was associated with 0.8 kg less weight gain. Increased carbohydrate intake from whole grains (0.4 kg less weight gain per 100 g/day increase), fruit (1.6 kg less weight gain per 100 g/day increase), and non-starchy vegetables (3.0 kg less weight gain per 100 g/day increase) was inversely associated with weight gain, whereas increased intake from refined grains (0.8 kg more weight gain per 100 g/day increase) and starchy vegetables (peas, corn, and potatoes) (2.6 kg more weight gain per 100 g/day increase) was positively associated with weight gain. In substitution analyses, replacing refined grains, starchy vegetables, and sugar sweetened beverages with equal servings of whole grains, fruit, and non-starchy vegetables was associated with less weight gain. The magnitude of these associations was stronger among participants with overweight or obesity compared with those with normal weight (P<0.001 for interaction). Most of these associations were also stronger among women.The findings of this study highlight the potential importance of carbohydrate quality and source for long term weight management, especially for people with excessive body weight. Limiting added sugar, sugar sweetened beverages, refined grains, and starchy vegetables in favor of whole grains, fruit, and non-starchy vegetables may support efforts to control weight.
Orthodontic appliances for the treatment of pediatric obstructive sleep apnea: A systematic review and network meta-analysis
Authors: Min Yu, Yanyan Ma, Ying Xu, Jingxuan Bai, Yujia Lu, Fang Han, Xuemei Gao
Journal: Sleep Medicine Reviews (2023)

This systematic review and network meta-analysis aims to preliminarily investigate the efficacy of different orthodontic appliances for the treatment of pediatric obstructive sleep apnea (OSA). Electronic databases were systematically searched. Randomized and non-randomized controlled trials with patients <18 y treated with either mandibular advancement appliance (MAA), rapid maxillary expansion (RME), or myofunctional therapy (MFT) were included. A network meta-analysis using multivariate random effects was conducted to estimate pooled differences using the apnea-hypopnea index (AHI) as the main outcome. Eleven studies (595 patients) were included in the analysis. Compared with control, MAA was associated with significant reductions in AHI of -2.18/h (95%CI -3.48 to -0.89, p = 0.001). Combined treatment of RME + adenotonsillectomy (AT) and RME + MAA showed a significant decrease in AHI, with -5.13/h (95%CI -7.50 to -2.76, p < 0.0001) and -3.79 (95%CI -5.21 to -2.37, p < 0.0001), respectively. MFT was associated with a -2.45/h (95%CI -4.76 to -0.14, p = 0.038) decrease in AHI. However, RME alone was not associated with significant AHI reduction (0.02, 95%CI -1.72 to 1.75, p = 0.985). The heterogeneity of the network meta-analysis was I2 = 32.6%. Limited evidence indicated that MAA (alone or combined with RME) and RME + AT were associated with benefits for pediatric patients with OSA. This study could not find convincing evidence of a significant benefit of other orthodontic appliances over control.
Validation of a real-time biliopancreatic endoscopic ultrasonography analytical device in China: a prospective, single-centre, randomised, controlled trial
Authors: Hui Ling Wu, Li Wen Yao, Hui Ying Shi, Lian Lian Wu, Xun Li, Chen Xia Zhang, Bo Ru Chen, Jun Zhang, Wei Tan, Ning Cui, Wei Zhou, Ji Xiang Zhang, Bing Xiao, Rong Rong Gong, Zhen Ding, Hong Gang Yu
Journal: The Lancet Digital Health (2023)

Endoscopic ultrasonography (EUS) is a key procedure for the diagnosis of biliopancreatic diseases. However, the performance among EUS endoscopists varies greatly and leads to blind spots during the operation, which can impair the health outcomes of patients. We previously developed an artificial intelligence (AI) device that accurately identified EUS standard stations and significantly reduced the difficulty of ultrasonography image interpretation. In this study, we updated the device (named EUS-IREAD) and validated its performance in improving the quality of EUS procedures.In this single-centre, randomised, controlled trial, we updated EUS-IREAD so it consisted of five learning models to identify eight EUS stations and 24 anatomical structures. The trial was done at the Renmin Hospital of Wuhan University (Wuhan, China) and included patients aged 18 years or older with suspected biliopancreatic (pancreas and biliopancreatic duct) lesions due to clinical symptoms, radiological findings, or laboratory findings, and with a high risk of pancreatic cancer. Patients were randomly assigned (1:1) by a dedicated research assistant using a computer-generated random number series (with a block size of four) to undergo the EUS procedure with or without the assistance of EUS-IREAD. Endoscopists in the EUS-IREAD-assisted group were required to observe all standard stations and anatomical structures according to the prompts by the AI device. Data collectors, the independent data anaylsis team, and patients were masked to group allocation. The primary outcome was the missed scanning rate of standard stations between the two groups, which was assessed in patients who underwent EUS procedure in accordance with the assigned intervention (per protocol). This trial is registered with ClinicalTrials.gov, NCT05457101.Between July 9, 2022, and Feb 28, 2023, 290 patients (mean age 55·93 years [SD 14·06], 152 [52%] male, and 138 [48%] female) were randomly assigned and analysed, including 144 in the EUS-IREAD-assisted group and 146 in the control group. The EUS-IREAD-assisted group had a lower missed scanning rate of stations than the control group (4·5% [SD 0·8] vs 14·3% [1·0], -9·8% [95% CI -12·2 to -7·5]; odds ratio 3·6 [95% Cl 2·6 to 4·9]; p<0·0001). No significant adverse event was found during the study.Our study confirms the capability of EUS-IREAD to monitor the blind spots and reduce the missed rate of stations and structures during EUS procedures. The EUS-IREAD has the potential to play an essential part in EUS quality control.Innovation Team Project of Health Commission of Hubei Province and College-enterprise Deepening Reform Project of Wuhan University.
Safety and durable immunogenicity of the TV005 tetravalent dengue vaccine, across serotypes and age groups, in dengue-endemic Bangladesh: a randomised, controlled trial
Authors: Mary-Claire R Walsh, Mohammed Shafiul Alam, Kristen K Pierce, Marya Carmolli, Masud Alam, Dorothy M Dickson, Dan M Bak, Sajia Afreen, Forida Nazib, Kibria Golam, Firdausi Qadri, Sean A Diehl, Anna P Durbin, Stephen S Whitehead, Rashidul Haque, Beth D Kirkpatrick
Journal: The Lancet Infectious Diseases (2023)
Sensitivity of the SARS-CoV-2 BA.2.86 variant to prevailing neutralising antibody responses
Authors: Daniel J Sheward, Yiqiu Yang, Michelle Westerberg, Sofia Öling, Sandra Muschiol, Kenta Sato, Thomas P Peacock, Gunilla B Karlsson Hedestam, Jan Albert, Ben Murrell
Journal: The Lancet Infectious Diseases (2023)
Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial
Authors: Luciano J Costa, Saurabh Chhabra, Eva Medvedova, Bhagirathbhai R Dholaria, Timothy M Schmidt, Kelly N Godby, Rebecca Silbermann, Binod Dhakal, Susan Bal, Smith Giri, Anita D'Souza, Aric C Hall, Pamela Hardwick, James Omel, Robert F Cornell, Parameswaran Hari, Natalie S Callander
Journal: The Lancet Haematology (2023)
A comparison of the NIRUDAK models and WHO algorithm for dehydration assessment in older children and adults with acute diarrhoea: a prospective, observational study
Authors: Adam C Levine, Monique Gainey, Kexin Qu, Sabiha Nasrin, Mohsena Bint-E Sharif, Syada S Noor, Meagan A Barry, Stephanie C Garbern, Christopher H Schmid, Rochelle K Rosen, Eric J Nelson, Nur H Alam
Journal: The Lancet Global Health (2023)

BackgroundDespite the importance of accurate and rapid assessment of hydration status in patients with acute diarrhoea, no validated tools exist to help clinicians assess dehydration severity in older children and adults. The aim of this study is to validate a clinical decision support tool (CDST) and a simplified score for dehydration severity in older children and adults with acute diarrhoea (both developed during the NIRUDAK study) and compare their accuracy and reliability with current WHO guidelines.MethodsA random sample of patients aged 5 years or older presenting with diarrhoea to the icddr,b Dhaka Hospital in Bangladesh between Jan 30 and Dec 13, 2022 were included in this prospective cohort study. Patients with fewer than three loose stools per day, more than 7 days of symptoms, previous enrolment in the study, or a diagnosis other than acute gastroenteritis were excluded. Patients were weighed on arrival and assessed separately by two nurses using both our novel clinical tools and WHO guidelines. Patients were weighed every 4 h to determine their percent weight change with rehydration, our criterion standard for dehydration. Accuracy for the diagnosis of dehydration category (none, some, or severe) was assessed using the ordinal c-index (ORC). Reliability was assessed by comparing the prediction of severe dehydration from each nurse's independent assessment using the intraclass correlation coefficient (ICC).Findings1580 patients were included in our primary analysis, of whom 921 (58·3%) were female and 659 (41·7%) male. The ORC was 0·74 (95% CI 0·71–0·77) for the CDST, 0·75 (0·71–0·78) for the simplified score, and 0·64 (0·61–0·67) for the WHO guidelines. The ICC was 0·98 (95% CI 0·97–0·98) for the CDST, 0·94 (0·93–0·95) for the simplified score, and 0·56 (0·52–0·60) for the WHO guidelines.InterpretationUse of our CDST or simplified score by clinicians could reduce undertreatment and overtreatment of older children and adults with acute diarrhoea, potentially reducing morbidity and mortality for this common disease.FundingUS National Institutes of Health.TranslationFor the Bangla translation of the abstract see Supplementary Materials section.
Carboplatin dosage: prospective evaluation of a simple formula based on renal function.
Authors: A H Calvert, D R Newell, L A Gumbrell, S O'Reilly, M Burnell, F E Boxall, Z H Siddik, I R Judson, M E Gore, E Wiltshaw
Journal: Journal of Clinical Oncology (2023)

A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates (GFR) in the range of 33 to 136 mL/min. Carboplatin plasma clearance was linearly related to GFR (r = 0.85, P less than .00001) and rearrangements of the equation describing the correlation gave the dosage formula dose (mg) = target area under the free carboplatin plasma concentration versus time curve (AUC) x (1.2 x GFR + 20). In a prospective clinical and pharmacokinetic study the formula was used to determine the dose required to treat 31 patients (GFR range, 33 to 135 mL/min) with 40 courses of carboplatin. The target AUC was escalated from 3 to 8 mg carboplatin/mL/min. Over this AUC range the formula accurately predicted the observed AUC (observed/predicted ratio 1.24 +/- 0.11, r = 0.886) and using these additional data, the formula was refined. Dose (mg) = target AUC x (GFR + 25) is now the recommended formula. AUC values of 4 to 6 and 6 to 8 mg/mL. min gave rise to manageable hematological toxicity in previously treated and untreated patients, respectively, and hence target AUC values of 5 and 7 mg/mL min are recommended for single-agent carboplatin in these patient groups. Pharmacokinetic modeling demonstrated that the formula was reasonably accurate regardless of whether a one- or two-compartment model most accurately described carboplatin pharmacokinetics, assuming that body size did not influence nonrenal clearance. The validity of this assumption was demonstrated in 13 patients where no correlation between surface area and nonrenal clearance was found (r = .31, P = .30). Therefore, the formula provides a simple and consistent method of determining carboplatin dose in adults. Since the measure of carboplatin exposure in the formula is AUC, and not toxicity, it will not be influenced by previous or concurrent myelosuppressive therapy or supportive measures. The formula is therefore applicable to combination and high-dose studies as well as conventional single-agent therapy, although the target AUC for carboplatin will need to be redefined for combination chemotherapy.
Zwitterionic polymers-armored amyloid-like protein surface combats thrombosis and biofouling
Authors: Xiaohui Mou, Wan Miao, Wentai Zhang, Wenxuan Wang, Qing Ma, Zeyu Du, Xin Li, Nan Huang, Zhilu Yang
Journal: Bioactive Materials (2023)

Proteins, cells and bacteria adhering to the surface of medical devices can lead to thrombosis and infection, resulting in significant clinical mortality. Here, we report a zwitterionic polymers-armored amyloid-like protein surface engineering strategy we called as "armored-tank" strategy for dual functionalization of medical devices. The "armored-tank" strategy is realized by decoration of partially conformational transformed LZM (PCTL) assembly through oxidant-mediated process, followed by armoring with super-hydrophilic poly-2-methacryloyloxyethyl phosphorylcholine (pMPC). The outer armor of the "armored-tank" shows potent and durable zone defense against fibrinogen, platelet and bacteria adhesion, leading to long-term antithrombogenic properties over 14 days
A twist in the tail: Of T cell subsets and disease
Authors: Shiv Pillai
Journal: The Journal of Experimental Medicine (2023)

In this issue of JEM, the work of Joachim et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20231028) on knockin mice with a specific tail mutation in LAT provides valuable insights about cytotoxic CD4+ T cells and human inflammatory diseases.
Reply to Kentaro Inamura’s Letter to the Editor re: Mingxiao Feng, Andres Matoso, Gabriel Epstein, et al. Identification of Lineage-specific Transcriptional Factor-defined Molecular Subtypes in Small Cell Bladder Cancer. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2023.05.023
Authors: Mingxiao Feng, Andres Matoso, Gabriel Epstein, Megan Fong, Yong Hyun Park, Andrew Gabrielson, Sunil Patel, Bagdan Czerniak, Eva Compérat, Jeannie Hoffman-Censits, Max Kates, Seungchan Kim, David McConkey, Woonyoung Choi
Journal: European Urology (2023)
Spatial and Temporal Mapping of Breast Cancer Lung Metastases Identify TREM2 Macrophages as Regulators of the Metastatic Boundary
Authors: Ido Yofe, Tamar Shami, Noam Cohen, Tomer Landsberger, Fadi Sheban, Liat Stoler-Barak, Adam Yalin, Truong San Phan, Baoguo Li, Lea Monteran, Ye'ela Scharff, Amir Giladi, Miriam Elbaz, Eyal David, Anna Gurevich-Shapiro, Chamutal Gur, Ziv Shulman, Neta Erez, Ido Amit
Journal: Cancer Discovery (2023)

Abstract Cancer mortality primarily stems from metastatic recurrence, emphasizing the urgent need for developing effective metastasis-targeted immunotherapies. To better understand the cellular and molecular events shaping metastatic niches, we used a spontaneous breast cancer lung metastasis model to create a single-cell atlas spanning different metastatic stages and regions. We found that premetastatic lungs are infiltrated by inflammatory neutrophils and monocytes, followed by the accumulation of suppressive macrophages with the emergence of metastases. Spatial profiling revealed that metastasis-associated immune cells were present in the metastasis core, with the exception of TREM2+ regulatory macrophages uniquely enriched at the metastatic invasive margin, consistent across both murine models and human patient samples. These regulatory macrophages (Mreg) contribute to the formation of an immune-suppressive niche, cloaking tumor cells from immune surveillance. Our study provides a compendium of immune cell dynamics across metastatic stages and niches, informing the development of metastasis-targeting immunotherapies. Significance: Temporal and spatial single-cell analysis of metastasis stages revealed new players in modulating immune surveillance and suppression. Our study highlights distinct populations of TREM2 macrophages as modulators of the microenvironment in metastasis, and as the key immune determinant defining metastatic niches, pointing to myeloid checkpoints to improve therapeutic strategies. This article is featured in Selected Articles from This Issue, p. 2489
Reply to Fabian Falkenbach, Francesco Sanguedolce, and Lars Budäus’s Letter to the Editor re: Elie Kaplan-Marans, Tenny R. Zhang, Jim C. Hu. Differing Recommendations on Prostate Biopsy Approach to Minimize Infections: An Examination of the European Association of Urology and American Urological Association Guidelines. Eur Urol. 2023;84:445–46
Authors: Elie Kaplan-Marans, Tenny R. Zhang, Jim C. Hu
Journal: European Urology (2023)
Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy
Authors: Daria Frank, Pradeep Kumar Patnana, Jan Vorwerk, Lianghao Mao, Lavanya Mokada Gopal, Noelle Jung, Thorben Hennig, Leo Ruhnke, Joris Maximillian Frenz, Maithreyan Kuppusamy, Robert Autry, Lanying Wei, Kaiyan Sun, Helal Mohammed Mohammed Ahmed, Axel Künstner, Hauke Busch, Heiko Müller, Stephan Hutter, Gregor Hoermann, Longlong Liu, Xiaoqing Xie, Yahya Al-Matary, Subbaiah Chary Nimmagadda, Fiorella Charles Cano, Michael Heuser, Felicitas Thol, Gudrun Göhring, Doris Steinemann, Jürgen Thomale, Theo Leitner, Anja Fischer, Roland Rad, Christoph Röllig, Heidi Altmann, Desiree Kunadt, Wolfgang E. Berdel, Jana Hüve, Felix Neumann, Jürgen Klingauf, Virginie Calderon, Bertram Opalka, Ulrich Dührsen, Frank Rosenbauer, Martin Dugas, Julian Varghese, Hans Christian Reinhardt, Nikolas von Bubnoff, Tarik Möröy, Georg Lenz, Aarif M. N. Batcha, Marianna Giorgi, Murugan Selvam, Eunice Wang, Shannon K. McWeeney, Jeffrey W. Tyner, Friedrich Stölzel, Matthias Mann, Ashok Kumar Jayavelu, Cyrus Khandanpour
Journal: Blood (2023)

Abstract Growth factor independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of hematopoiesis. GFI1-36N is a germ line variant, causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10% to 15% among patients with acute myeloid leukemia (AML) and 5% to 7% among healthy Caucasians and promotes the development of this disease. Using a multiomics approach, we show here that GFI1-36N expression is associated with increased frequencies of chromosomal aberrations, mutational burden, and mutational signatures in both murine and human AML and impedes homologous recombination (HR)–directed DNA repair in leukemic cells. GFI1-36N exhibits impaired binding to N-Myc downstream-regulated gene 1 (Ndrg1) regulatory elements, causing decreased NDRG1 levels, which leads to a reduction of O6-methylguanine-DNA-methyltransferase (MGMT) expression levels, as illustrated by both transcriptome and proteome analyses. Targeting MGMT via temozolomide, a DNA alkylating drug, and HR via olaparib, a poly-ADP ribose polymerase 1 inhibitor, caused synthetic lethality in human and murine AML samples expressing GFI1-36N, whereas the effects were insignificant in nonmalignant GFI1-36S or GFI1-36N cells. In addition, mice that received transplantation with GFI1-36N leukemic cells treated with a combination of temozolomide and olaparib had significantly longer AML-free survival than mice that received transplantation with GFI1-36S leukemic cells. This suggests that reduced MGMT expression leaves GFI1-36N leukemic cells particularly vulnerable to DNA damage initiating chemotherapeutics. Our data provide critical insights into novel options to treat patients with AML carrying the GFI1-36N variant.
Time to Think about HLA-Based Diagnostics in Lung Cancer?
Authors: Anastasios Dimou
Journal: Clinical Cancer Research (2023)

Summary HLA evolutionary divergence reflects the ability to recognize diverse neoantigens as non-self, and as a biomarker is conceptually distinct from programmed cell death ligand 1 expression and tumor mutation burden. HLA-based assays to predict benefit from immunotherapy in lung cancer require prospective validation. See related article by Jiang et al., p. 4830
A human genome editing–based <i>MLL</i>::<i>AF4</i> ALL model recapitulates key cellular and molecular leukemogenic features
Authors: Clara Bueno, Raul Torres-Ruiz, Talia Velasco-Hernandez, Oscar Molina, Paolo Petazzi, Alba Martinez, Virginia Rodriguez, Meritxell Vinyoles, Sandra Cantilena, Owen Williams, Nerea Vega-Garcia, Sandra Rodriguez-Perales, Jose C. Segovia, Oscar Quintana-Bustamante, Anindita Roy, Claus Meyer, Rolf Marschalek, Alastair L. Smith, Thomas A. Milne, Mario F. Fraga, Juan Ramón Tejedor, Pablo Menéndez
Journal: Blood (2023)

Cellular ontogeny and MLL breakpoint site influence the capacity of MLL-edited CD34+ hematopoietic cells to initiate and recapitulate infant patients' features in pro-B-cell acute lymphoblastic leukemia (B-ALL). We provide key insights into the leukemogenic determinants of MLL-AF4+ infant B-ALL.